We have established a protein chemistry facility that is overseen by the principal investigator and that now routinely does analyses for more than 100 different laboratories at Yale, the N.I.H. and 26 other universitiest. The Yale Facility has already demonstrated that it can successfully serve the needs of a diverse group of investigators whose problems require either peptide separation, amino acid sequence or analysis, or peptide synthesis. Amino acid sequencing of peptides isolated from enzymatic digests of sub-nanomole amounts of protein has, in particular, become one of the most essential services offered in our facility. To meet the exponentially increasing demand for this service, funds are requested to purchase an Applied Biosystems Pulsed- Liquid Protein Sequencer. The faster cycle time and higher repetitive yield of this instrument, compared to other automated sequences currently available, will allow our facility to both keep pace with the growing need for amino acid sequence data and to also significantly improve our capability to determine long stretches of sequence. Most of the protein and peptide sequencing done in our facility is directed at obtaining amino acid sequences that can serve as the basis for synthesizing oligonucleotide probes that can then be used to clone the respective gene. Once the cDNA clone is isolated it can then be sequenced. The difficulties involved in trying to automate DNA sequencing have so far discouraged our facility from offering DNA sequencing as a service. The Applied Biosystems DNA Sequencing System overcomes these limitations and offers the possibility of automatically sequencing 6,000 bases per day. This high degree of automation is clearly essential to adequately handle the increasing quantity of DNA sequencing that is required in eukaryotic systems. If funds are provided, these two instruments will immediately be brought to bear on a number of biomedically important research projects that range from inherited diseases to molecular parasitology to understanding the mechanism of synaptic transmission. Our facility has the technical expertise that is necessary to ensure that these instruments are maintained and operated continuously at peak efficiency. The potential impact of these two instruments on biomedical research at Yale, the N.I.H., as well as several other universities is indeed great.